Metabotropic Glutamate Receptors Classification Sample Clauses

Metabotropic Glutamate Receptors Classification. To date, eight members of the G-protein-coupled metabotropic glutamate receptor family have been identified (mGluR1–8) which have been divided on the basis of sequence homology, second messenger coupling and pharmacology into three groups: group I (mGluR1 and 5), group II (mGluR2 and 3) and group III (mGluR4, 6, 7, 8). Compared to the effect of ionotropic receptors, the activation of mGluRs leads to a slower and longer lasting effect on cellular excitability. Thus, mGluRs have the capacity to provide a mechanism by which glutamate can modulate or fine-tune activity at the same synapses at which it elicits fast synaptic responses through ionotropic receptors. The mGluRs have seven trans-membrane domains with an extracellular N-terminal and intracellular COOH terminal. They display little sequence homology with other metabotropic receptors, except for a modest resemblance to GABAB receptors. However, mGluRs of the same group show about 70% sequence identity, whereas between groups this percentage decreases to about 45% (Conn and Pin, 1997). This classification is also supported by the respective transduction mechanisms of the different mGluR subtypes. The group I mGluRs predominantly couple via Gq/G11 to phospholipase C, whereas the group II and group III receptors couple with Gi/Go to inhibit adenylyl cyclase activity. Although mGluR family members can mediate synaptic transmission via activation of slow excitatory postsynaptic potentials, they generally exert a more modulatory role, regulating neuronal excitability, synaptic transmission and plasticity. mGluR-mediated signalling is achieved both via the activation of intracellular second messenger pathways and subsequent regulation of downstream effectors, and through the direct action of the βγ subunits of the heterotrimeric G protein (Anwyl, 1999). Distribution studies have shown mGluR mRNA and protein expression in many cortical and subcortical regions of the CNS. The striatum is enriched in all mGluR subtypes, except for mGluR6 which is solely expressed in the retina (Duvoisin et al., 2005).